The role of vanadium bromoperoxidase in the biosynthesis of halogenated marine natural products

Halogenated natural products are frequently reported metabolites in marine seaweeds. These compounds span a range from halogenated indoles, terpenes, acetogenins, phenols, etc., to volatile halogenated hydrocarbons that are produced on a very large scale. In many cases these halogenated marine metabolites possess biological activities of pharmacological interest. Given the abundance of halogenated marine natural products found in marine organisms and their potentially important biological activities, the biogenesis of these compounds has intrigued marine natural product chemists for decades. Over a quarter of a century ago, a possible role for haloperoxidase enzymes was first suggested in the biogenesis of certain halogenated marine natural products, although this was long before haloperoxidases were discovered in marine organisms. Since that time, FeHeme- and Vanadium-haloperoxidases (V-HPO) have been discovered in many marine organisms. The structure and catalytic activity of vanadium haloperoxidases is reviewed herein, including the importance of V-HPO-catalyzed bromination and cyclization of terpene substrates.     

A near-infrared Fourier transform Raman spectroscopy of epidermal keratinocytes: changes in the protein-DNA structure following malignant transformation

We report here the use of near-infrared (NIR) Fourier transform (FT) Raman spectroscopy to analyze normal human epidermal keratinocytes prior to and following malignant transformation. Our analysis indicates specific Raman spectral differences between immortalized (HPK1A) and malignant ras transformed (HPK1A-ras) cells. In addition, striking spectral differences are seen in the DNA isolated from these cells and particularly in the 843/810 cm(-1) ratio with values of 1.6 +/- 0.13 in HPK1A cells and 0.68 +/- 0.09 in HPK1A-ras cells (mean +/- S.D., n = 12, P < 0.001) indicating specific alterations in the backbone conformation markers following malignant transformation. Subsequently, we analysed the effect of a strong inhibitor of keratinocyte growth, the Vitamin D analog EB1089, on the Raman spectra of intact cells and on the 843/810 cm(-1) ratio in the DNA isolated from both cell lines. Specific changes were observed in intact cells in the 1300-750 cm(-1) region. Furthermore, the 843/810 cm(-1) ratio of isolated DNA from HPK1A cells was not affected by EB1089 but significantly increased in DNA isolated from HPK1A-ras cells so much that it became closer to the value observed for HPK1A cells (1.07 +/- 0.10). Our data suggest that Raman analysis of DNA and in particular the 843/810 cm(-1) ratio can provide useful indices of malignant transformation and efficacy of anticancer agents.     

The synthesis,structural characterization and biological evaluation of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives as potential anticancer agents

A series of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i and 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N‐(fluorobenzoyl) amino acid derivatives using the standard N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride, 1‐hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L‐alanine. All of the compounds were fully characterized using a combination of ¹H NMR, ¹³C NMR, ¹⁹F NMR, distortionless enhancement by polarization transfer (DEPT)‐135, ¹H–¹H correlation spectroscopy (COSY) and ¹H–¹³C COSY (heteronuclear multiple‐quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen‐positive MCF‐7 breast cancer cell line. Compounds 4g , 4i , 5h and 5i exhibited cytotoxic effects on the MCF‐7 breast cancer cell line. N‐(Ferrocenylmethyl‐L‐alanine)‐3,4,5‐trifluorobenzene‐carboxamide ( 5h ) was the most active compound, with an IC₅₀ value of 2.84 μm . Compounds 4i , 5h and 5i had lower IC₅₀ values than that found for the clinically employed anticancer drug cisplatin (IC₅₀ = 16.3 μm against MCF‐7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species‐mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd.     

Direct observations of the leaching of a simulated nuclear waste glass in a radiation environment

The durability of the media proposed for the containment of commercial nuclear waste will be affected not only by the differences in groundwater composition that they might encounter but also by the changes that their own irradiation fields will make to these solutions. Experimental results that question the ability of current leaching experiments to predict the stability of nuclear waste composites are presented.     

Synthesis of 2-C-methylerythritols and 2-C-methylthreitols via enantiodivergent Sharpless dihydroxylation of trisubstituted olefins

The mevalonate-independent pathway (MIP) is an interesting avenue for antimicrobial lead discovery. Here, we present a unified enantioselective synthesis of all four stereoisomers of 2-C-methyltetrol. These are useful building blocks of many bioactive natural products, including 2-C-methylerythritol phosphate (MEP) of the MIP biosynthetic pathway.     

Characterization of the Charge Transfer Complex from Furan and Maleic Anhydride and the Alternating Copolymer

A previously unreported copolymer between furan and maleic anhydride was readily obtained by free radical initiation of benzene solutions of the comonomers. The product copolymers exhibit remarkably uniform composition regardless of monomer feed ratios. A donor-acceptor complex was suspected to account for the 1:1 alternating sequence of the monomers in the product. The complex was easily detected and partially characterized, although its exact role in the mechanism is uncertain.     

Studies in Cyclocopolymerization. X. Cyclocopolymerization of Tetrahydronaphthoquinone and Dimethyl Tetrahydronaphthoquinone with Divinyl Ether

Abstract

Tetrahydronaphthoquinone (THNQ) and dimethyl tetrahydronaphthoquinone (DMTHNQ) were found by UV spectroscopy to form donor-acceptor complexes with divinyl ether (DVE), the latter being the electron donor. Since the participation of such complexed species has been considered in the cyclocopolymerization of a 1,4-diene with a monoolefin such as DVE-maleic anhydride (MA) and DVE-fumaronitrile (FN) systems, radical copolymerization of THNQ and DMTHNQ with DVE was studied. It was found that these copolymers have constant 1:1 composition regardless of the feed composition. The terpolymerization of DVE-THNQ-DMTHNQ confirmed the 1:1 donor-acceptor composition in the polymer. The integration of the NMR spectrum was used in determining the copolymer composition. The spectroscopic data suggest a cyclized repeating unit in which the copolymer main chain consists of only DVE units. There is a marked difference between these copolymers and the typical cyclo-copolymers, such as DVE-MA and DVE-FN, in which the copolymer main chains consist of DVE and the comonomer alternately, with the overall composition being 1:2. These results are interpreted in terms of the steric effect by the bulky acceptor monomers and the electronic interaction between the comonomers. The competition between an acceptor monomer and the charge-transfer (CT) complex toward the cyclized DVE radical in the propagation step appears to favor the CT complex.     

The Fundamental Basis for Cyclopolymerization. VII. A Cyclopolymerization Study of Certain Allylcycloalkenes

The cyclopolymerization characteristics of 3-allylcyclopentene, 3 allylcyclopentene, 3-allylcyclohexene, and 4-allylohexene were studied and the extent of their cyclopolymerization by cationic initiation were compared with previously reported solvolysis results involving the same intermediate carbonium ion. The results of this study were also compared with previously reported results on 4-vinylcyclohexene and 1, 4-dimethylenecyclohexane. The allylcycloalkenes were also polymerized by metal alkyl coordination catalysts and the extent of cyclization in each case was determined. The polymers derived from these monomers invariably contained polymeric fractions (27 to 99%) which were soluble in non-polar organic solvents. Calculations based on NMR spectral data indicated the cationic polymers were 68 to 95% cyclized. The extent of cyclization was found to parallel the interolefinic separation in the monomer. Coordination polymerization yielded somewhat lower ratios of cyclizations (54 to 80%) in all cases except for 4-allylcyclohexene. 4-Allylcyclohexene gave only 5 to 54% cyclization, 4-Vinylcyclohexene, 3-allylcyclopentene, and 3-allylcyclohexene produced soluble copolymers with maleic anhydride. Elemental analysis indicated the composition of these copolymers to be 2:1 molar in maleic anhydride and diene units. A cyclic copolymerization mechanism suggested the formation of a multicyclic repeating unit. The other monomers gave crosslinked polymers since maleic anhydride could not be incorporated into a six-membered ring.